We propose to develop a new intervention model directed toward the coordination and simplification of HIV treatment which has particular relevance to older persons and other, less mobile, populations. This model relies on the development of a novel Bio-nanosensor (BNS) diagnostic/treatment monitoring technology that will provide both health workers as well as patients with important medical information regarding disease status on a real-time basis in the home setting. This new technology will enable the creation of a new HIV/AIDS management system that will result in more efficient and effective monitoring and treatment of HIV infection and its complications. These goals are achieved through the following specific aims: Specific Aim 1: Develop a Novel Piezoelectric Bio-nanosensor Device to Detect HIV In this specific aim, we propose to develop a piezoelectric Bio-nanosensor (BNS) device for the rapid (10-15 min) fluid-phase detection of HIV based on the presence of the biomarkers gp120 and p24, and of intact HIV virus. We will then optimize assay sensitivity, specificity and dynamic range, and validation this device against the current laboratory-based ELISA/SPR detection format. Milestone: The development of a piezoelectric BNS assay with the ability to detect gp120 and p24 in <15 min reaction time with a limit of detection <100 pg/ml, while using no more than 10 -100 <l of fluid sample. Specific Aim 2: Design and Develop a BNS assay for Multiple Biomarkers Associated with HIV/AIDS Once the design of the basic BNS device format and HIV detection methods are established in Specific Aim 1, we will develop individual biochips optimized for sensing additional biomarkers that are routinely assessed in HIV infected patients: including CD4, insulin, C-peptide, IL-6 and HbA1C, and apply these to blood and serum analysis. This BNS assay will thus provide a specific health profile of HIV/AIDS patients. BNS optimization will include determining individual reaction conditions for each biomarker, and relevant operating conditions such as: size of electrode, packing density, optimum dimensions, acoustic mode of interaction, software and hardware development for monitoring multiple sensors and signal processing. Milestone: Development of a BNS system for simultaneous detection of the biomarkers gp120, p24, CD4, insulin, C-peptide, IL-6 and HbA1C at picogram sensitivity with an anticipated assay cost of $5 - $10/sample PUBLIC HEALTH RELEVANCE: Current care strategies for older patients (the number of older persons with HIV infection is forecast to augment in the years to come) with HIV infection as well as other conditions face challenges associated with highly complex treatment paradigms that lack coordination and thus often render care less effective. With multiple drugs and multiple problems, such patients are forced to endure a lower quality of life marked by the high possibility of treatment complications and diminished medical outcomes. In order to address this need, we propose an intervention model (an original bio-nanosensor detection technology) directed toward the coordination and simplification of HIV treatment, particularly in older persons suffering from multiple conditions.